Autocrine abscisic acid plays a key role in quartz-induced macrophage activation

作者：Magnone Mirko^*; Sturla Laura; Jacchetti Emanuela; Scarfi Sonia; Bruzzone Santina; Usai Cesare; Guida Lucrezia; Salis Annalisa; Damonte Gianluca; De Flora Antonio; Zocchi Elena

来源：The FASEB Journal, 2012, 26(3): 1261-1271.

DOI：10.1096/fj.11-187351

• inflammation
• NF kappa B
• TNF alpha
• PGE(2)
• LANCL2

Inhalation of quartz induces silicosis, a lung disease where alveolar macrophages release inflammatory mediators, including prostaglandin-E-2 (PGE(2)) and tumor necrosis factor alpha (TNF-alpha). Here we report the pivotal role of abscisic acid (ABA), a recently discovered human inflammatory hormone, in silica-induced activation of murine RAW264.7 macrophages and of rat alveolar macrophages (AMs). Stimulation of both RAW264.7 cells and AMs with quartz induced a significant increase of ABA release (5- and 10-fold, respectively), compared to untreated cells. In RAW264.7 cells, autocrine ABA released after quartz stimulation sequentially activates the plasma membrane receptor LANCL2 and NADPH oxidase, generating a Ca2+ influx resulting in NF kappa B nuclear translocation and PGE(2) and TNF-alpha release (3-, 2-, and 3.5-fold increase, respectively, compared to control, un-stimulated cells). Quartz-stimulated RAW264.7 cells silenced for LANCL2 or preincubated with a monoclonal antibody against ABA show an almost complete inhibition of NF kappa B nuclear translocation and PGE(2) and TNF-alpha release compared to controls electroporated with a scramble oligonucleotide or preincubated with an unrelated antibody. AMs showed similar early and late ABA-induced responses as RAW264.7 cells. These findings identify ABA and LANCL2 as key mediators in quartz-induced inflammation, providing possible new targets for antisilicotic therapy.-Magnone, M., Sturla, L., Jacchetti, E., Scarf, S., Bruzzone, S., Usai, C., Guida, L., Salis, A., Damonte, G., De Flora, A., Zocchi, E. Autocrine abscisic acid plays a key role in quartz-induced macrophage activation. FASEB J. 26, 1261-1271 (2012). www.fasebj.org

• 出版日期2012-3